Molecular and Cellular Mechanisms of Myocardial Ischemia and Reperfusion Injury: A Narrative Review

TL;DR

This review explains how reduced blood flow and subsequent reperfusion damage heart cells, highlighting key molecular and cellular processes involved in heart injury.

Contribution

The paper provides a comprehensive overview of the molecular and cellular mechanisms underlying myocardial ischemia and reperfusion injury.

Findings

Ischemia causes ATP depletion and calcium overload in cardiomyocytes.

Reperfusion leads to oxidative stress, inflammation, and cell death via mitochondrial dysfunction.

Targeting mPTP and ROS could reduce reperfusion injury and improve heart recovery.

Abstract

Myocardial ischemia represents a state of reduced coronary perfusion with oxygenated blood, insufficient to meet the metabolic demands of the myocardium. Both acute and chronic ischemia trigger a cascade of cellular events that lead to disturbances in ionic balance, mitochondrial function and energy metabolism. During ischemia, cardiomyocytes (CMs) shift from aerobic to anaerobic metabolism, resulting in adenosine triphosphate (ATP) depletion, loss of ionic homeostasis and calcium (Ca2+) overload that activate proteases, phospholipases and membrane damage. Reperfusion restores oxygen supply and prevents irreversible necrosis but paradoxically initiates additional injury in marginally viable myocardium. The reoxygenation phase induces excessive production of reactive oxygen species (ROS), endothelial dysfunction and a strong inflammatory response mediated by neutrophils, platelets and cytokines. Mitochondrial dysfunction and opening of the mitochondrial permeability transition pore (mPTP) further amplify oxidative stress and inflammation and trigger apoptosis and necroptosis. Understanding these intertwined cellular and molecular mechanisms remains essential for identifying novel therapeutic targets aimed at reducing reperfusion injury and improving myocardial recovery after ischemic events.

Figures